This is an interdisciplinary study involving immunology and psychology. It will examine the nature of the relationship between emotionality in mice and immune system function. Specifically, the biological basis for the observation that a behavioral measure of emotionality is highly correlated with T cell levels in the bone marrow will be explored. The existing evidence leads us to believe that the correlation between these measures lies either at the level of the hypothalamic-pituitary-adrenal cortical axis or at the level of the T cell-vascular endothelium interaction. Corticosteroid levels will be manipulated by adrenalectomy, stress or cortisol administration, and effects on T cell distribution measured by mitogen response, immunofluorescence and radioisotope tracer studies. Congenic mice with behavior differences will be used to identify genetic loci responsible for behavior and T cell distribution, and to discover if these differences are reflected in T cell subpopulations and B cells. Once the nature of the connection between behavior and immune system function is established, we will determine whether modification of emotional responsiveness, either by changing early life experiences or by learning to cope with stress, can also modify immune system function. These studies will form the basis for a more rational approach to the mind/immune system nexus in humans.